Hematologic dysfunction in Lassa fever

Abstract

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) greater than 150 IU/L or viremia of greater than 10(3.6) tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST less than 150 IU/L or viremia, less than 10(3.6)TCID50/ml), (P less than 0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P less than 0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P less than 0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P less than 0.0035 in response to ADP and P = 0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P = 0.0013 for ADP and P less than 0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemorrhagic fever occurs after intravenous, but not after intragastric, inoculation of rhesus macaques with lymphocytic choriomeningitis virus

“…We also observed a dramatic drop in platelet numbers in the two i.v.-inoculated monkeys. It is notable that this thrombocytopenia is more severe in the rhesus LCMV-WE infection than in rhesus infections with Lassa virus [Fisher-Hoch et al, 1988] (also P. Jahrling, unpublished observations). It is unclear whether the thrombocytopenia is due to lack of bone marrow production, increased megakaryocyte/platelet destruction, or increased sequestration in tissues.…”

“…Unlike the filoviruses, Marburg and Ebola, that destroy vascular endothelial cells in culture [Schnittler et al, 1993;Feldmann et al, 1996;Yang et al, 1998;Baize et al, 1999], arenaviruses like Lassa fever virus do not destroy cultured endothelial cells, but do diminish their capacity to express chemokines [Fisher-Hoch et al, 1987;Schnittler et al, 1993;Lukashevich et al, 1999]. Also unlike Ebola and Marburg hemorrhagic disease, Lassa fever disease does not cause an increase in fibrinogen breakdown products or diffuse intravascular coagulation (DIC) [Fisher-Hoch et al, 1988]. With Lassa, there is a defect in platelet aggregation that corresponds to severity of disease [Cummins et al, 1989a,b]; however, platelet and fibrinogen turnover rates are normal in experimental primate infections [Fisher-Hoch et al, 1987].…”

Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells

“…Contaminating genomic DNA was digested with DNase I (Qiagen) during the extraction procedure. First-strand cDNA was synthesized from 200 ng of RNA, using Superscript II reverse transcriptase (Life Technologies) and oligo(dT) (15) (Life Technologies); 10% of the products of this reaction were used as a template for qualitative and real-time PCR. We checked for the absence of genomic DNA amplification for each gene by adding RNA directly to the amplification mixture without reverse transcription.…”

“…In contrast, severe LV infections seem to be associated with high levels of viremia and immunosuppression. Structural changes, the cellular depletion of secondary lymphoid tissues, necrosis of the splenic marginal zone, transitory lymphopenia, and the abolition of mitogenic T cell proliferation have been described in patients and nonhuman primates (7,14,15). The infection of MP in vitro leads to the release of viral particles, but not to an increase in the synthesis of TNF-␣ and IL-8 (9).…”

Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus

“…Elevated viremia and immunosuppression seem to characterize severe LV infections. Other features observed in patients and nonhuman primates (NHP) include structural changes, cellular depletion of secondary lymphoid tissues, necrosis of the splenic marginal zone, transitory lymphopenia, and abolition of mitogenic T-cell proliferation (7,25,27,28).…”